A catechol-''O''-methyltransferase (COMT) inhibitor is a drug that inhibits the enzyme catechol-''O''-methyltransferase. This enzyme methylates

catecholamines A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a substi ...

such as

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

. It also methylates

levodopa -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...

. COMT inhibitors are indicated for the treatment of

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

in combination with levodopa and an

aromatic L-amino acid decarboxylase inhibitor An aromatic L-amino acid decarboxylase inhibitor (synonyms: DOPA decarboxylase inhibitor, Extracerebral decarboxylase inhibitor, DDCI and AAADI) is a medication of type enzyme inhibitor which inhibits the synthesis of dopamine by the enzyme ar ...

(e.g.

carbidopa Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–br ...

benserazide Benserazide (also called Serazide or Ro 4-4602) is a peripherally acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood–brain barrier. It is on the World Health Organization's List of ...

). The therapeutic benefit of using a COMT inhibitor is based on its ability to prevent the methylation of levodopa to 3-''O''-methyldopa, thus increasing the bioavailability of levodopa. COMT inhibitors significantly decrease off time in people with Parkinson's disease also taking

carbidopa/levodopa Carbidopa/levodopa, also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa. It is primarily used to manage the symptoms of Parkinson's disease, but it does not slow down the disease or stop it ...

List of COMT inhibitors

entacapone Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinson's disease. Entacapone together with levodopa and carbidopa allows levodopa to have a l ...

(Comtan, Comtess, Stalevo) *nebicapone *

nitecapone Nitecapone (INN; OR-462) is a drug which acts as a selective inhibitor of the enzyme catechol ''O''-methyl transferase (COMT). It was patented as an antiparkinson medication but was never marketed. See also * Catechol-O-methyltransferase inh ...

opicapone Opicapone, sold under the brand name Ongentys, is a medication which is administered together with levodopa in people with Parkinson's disease. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor. The most common side effects are dys ...

(Ongentys) *

tolcapone Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinson's disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-''O''-methyltransferase (COMT). It has demonstrat ...

(Tasmar) Entacapone and opicapone are peripheral inhibitors, unable to cross the blood-brain barrier. Tolcapone is able to cross the blood-brain barrier. Tolcapone has been associated with at least three fatal cases of

acute liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...

and is thus only rarely prescribed. Patients taking tolcapone must be monitored for hepatic failure. Entacapone and opicapone have not been associated with hepatotoxicity.

Adverse effects

* nausea * orthostatic hypotension * vivid dreams * confusion * hallucinations * hepatotoxicity (only tolcapone) * diarrhea * drowsiness * urine discoloration * dyskinesia

References

Catechol-O-methyltransferase inhibitors {{nervous-system-drug-stub